With Taxol, chromosomes divide and get conquered

New mechanism discovered for decades-old cancer drug

MIXED UP Human breast cancer cells from women treated with the chemotherapy drug paclitaxel abnormally split into more than two cells (shown in a micrograph, with alpha-tubulin, a protein involved in cell division, in red and DNA in blue). The progeny cells have jumbled chromosomes and tend to die.

Lauren M. Zasadil and B. A. Weaver

By Tina Hesman Saey

March 26, 2014 at 4:29 pm

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A popular cancer drug has previously undiscovered tricks up its sleeve.

The best-selling chemotherapy drug paclitaxel (Taxol) treats breast, lung, ovarian and other cancers. Animal studies and experiments on human cells in lab dishes had suggested the drug worked by freezing cells in the act of dividing. But those studies used drug doses much higher than tumor cells in a patient’s body would encounter.

So Beth Weaver of the University of Wisconsin–Madison and colleagues measured drug levels in breast tumors taken from women who had been treated with paclitaxel before surgery. Instead of stopping cell division, low, clinically relevant doses of the drug caused cells to pull their chromosomes in multiple directions, the researchers found. Cells caught in the multidirectional tug-of-war died after the split because their chromosomes had been scrambled, Weaver’s team reports in the March 26 Science Translational Medicine.

Knowing how paclitaxel really works may help doctors better predict who will benefit from the drug. The understanding may also aid researchers in designing more effective versions of the drug.

PULLED APART A human breast cancer cell treated with the drug paclitaxel attempts to divide. Scientists have learned that, instead of halting cell division, the drug causes chromosomes (red) to be pulled in multiple directions. The tug-of-war scrambles the cells’ DNA and leads to cell death. Credit: Lauren M. Zasadil and B.A. Weaver